T-Cells to Control the Graft-Versus-Host Effect of Nonmyeloablative Hematopoietic Cell Transplantation
The aim of this project is to develop T cells to help further reduce the toxicity of bone marrow transplantation. Bone marrow transplantation, also known as hematopoietic cell transplantation, is the only curative treatment available for many patients with passive apostraphe leukemia and lymphoma. Using the dog model of bone marrow transplantation, Dr. Georges’ laboratory has recently pioneered the development of a clinically successful type of hematopoietic cell transplantation that uses substantially lower and less toxic doses of chemotherapy and radiation to treat patients with leukemia and lymphoma. To further improve upon the success of this low-dose non-toxic treatment for patients with leukemia and lymphoma, they want to study if T cells can be engineered to specifically help the donor marrow graft attack the blood cells containing leukemia or lymphoma without attacking the rest of the patient. The dog model of transplantation has been an excellent tool for the study of bone marrow transplantation and has been the basis for the successful translation of much laboratory research to the clinic. In this project Dr. Georges proposes to study T cells from the bone marrow donor dogs, grown in the laboratory, that are especially trained to recognize the recipient’s blood and immune cells. The recipient dogs will have marrow and blood cell production that is a combination of part donor and part recipient. After infusion into the recipient dog, the first aim will be to ask if the laboratory-grown donor T cells can eliminate the recipient’s residual blood and immune system cells. This would serve as a model for eradication of a patient’s leukemia or lymphoma cells. In the second set of experiments, the donor T cells will be genetically modified to make them safer with respect to graft-versus-host disease. If this strategy is successful in the dog, Dr. Georges and his team will then be able to study if the dose of radiation/chemotherapy can be further decreased to make bone marrow transplantation for patients with leukemia and lymphoma even less toxic yet much more effective.